OSIBOOST 2: Improving Osimertinib cost-effectiveness in Non-Small Cell Lung Cancer treatment using dose-modification and pharmacokinetic boosting with cobicistat

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Hospital Maastricht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

16 Jul 2024 → ongoing

Decision date (initial)

2024-01-25

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMW

External identifiers

EU CT number

2023-505700-35-00

ClinicalTrials.gov

NCT05748093

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacoeconomic

This study will consist of two sub-studies in patients with advanced EGFR mutated NSCLC. Depending on disease status, patients may be enrolled in sub-study A (stable disease or better) or B (CNS oligoprogression):

OSIBOOST 2-A: is a single-arm near-equivalence study, intended to assess the clinical feasibility of a modified osimertinib dosing strategy combining therapeutic drug monitoring, osimertinib dose-modification and pharmacokinetic (PK) boosting, in order to improve osimertinib cost-effectiveness and reduce toxicity while maintaining clinical efficacy. This study will include patients with advanced EGFR positive NSCLC who are treated with osimertinib as part of regular care. The primary objective is to evaluate the clinical feasibility of a modified osimertinib dosing strategy to allow for a personalized, more cost-effective osimertinib dosing schedule while maintaining osimertinib exposure within the provisional, clinically-proven, therapeutic window (125 – 259 ng/mL).

OSIBOOST 2-B: is an exploratory single-arm pharmacokinetic boosting study, designed to assess whether PK boosting provides a viable therapeutic option in patients with asymptomatic central nervous system (CNS) oligoprogression. The primary objective is to assess whether boosting standard (unaltered) osimertinib treatment can result in renewed CNS disease control, as a cost-effective alternative for off-label, non-reimbursable, dose-escalation to 160 mg osimertinib once daily (QD).

Secondary objectives 5

1. Evaluating cost-effectiveness (CEA) of the modified osimertinib treatment versus the standard-of-care.
2. Evaluating clinical efficacy (OSIBOOST 2-A: progression-free survival, OSIBOOST 2-B: DCR at 12 weeks).
3. Further evaluating the safety profile of osimertinib/cobicistat concomitant treatment.
4. Evaluating pharmacokinetic parameters of Osimertinib, Cobicistat and the active Osimertinib metabolite AZ5104.
5. Evaluating the effect of CYP3A genotype on osimertinib exposure.

Conditions and MedDRA coding

Non-Small Cell Lung Cancer with an EGFR driver mutation.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. The patient receives osimertinib 80 mg once daily as part of their standard treatment plan.
2. The patient has a World Health Organisation (WHO) Performance Status (PS) of 0-2.
3. The patient is 18 years or older.
4. The patient is able and willing to sign informed consent.
5. The patient is able and willing to undergo additional blood sampling (e.g. for therapeutic drug monitoring).
6. The patient consents to their blood being analysed for CYP3A-genotype.
7. OSIBOOST 2-A: the patient has non-squamous advanced EGFR-mutated NSCLC with no signs of imminent progression (CT-confirmed). If the patient does have signs of progression, they are only eligible if their treating physician deems treatment beyond progression to be appropriate.
8. OSIBOOST 2-B: the patient has non-squamous EGFR-mutated NSCLC with radiologically confirmed (RANO-progressive) asymptomatic intracranial progression, not in an eloquent area. Furthermore, extracranial disease should be controlled (no RECIST v1.1 progression).

Exclusion criteria 4

1. The patient is taking any other drug or herbal substance which 1) is known to strongly inhibit CYP3A, P-gp or BCRP activity; 2) is primarily metabolized by CYP3A, P-gp or BCRP and has a small therapeutic range; or 3) may otherwise affect CYP3A, P-gp or BCRP metabolic activity.
2. The patient has impaired gastrointestinal function that may alter the absorption of osimertinib or cobicistat (e.g. ulcerative disease, uncontrolled nausea or vomiting, malabsorption syndrome, small bowel resection).
3. The patient has chronic liver disease (Child-Pugh score: class C).
4. The patient is either pregnant or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. OSIBOOST 2-A: The daily cumulative dose reduction accomplished in individual patients, while retaining osimertinib exposure (i.e. osimertinib trough (Cmin,SS) levels within the specified provisional therapeutic range (125 – 259 ng/mL).
2. OSIBOOST 2-B: CNS disease control rate (DCR) at 12 weeks.

Secondary endpoints 7

1. Osimertinib and AZ5104 trough concentrations in plasma during steady state
2. Number of (Serious) Adverse Events and Suspected Unexpected Serious Adverse Reaction events during trial course and follow-up.
3. OSIBOOST 2-A: Average osimertinib intake reduction over time.
4. Progression-Free Survival (PFS) during osimertinib/cobicistat concomitant treatment.
5. CYP3A genotype.
6. OSIBOOST 2-B: Trough concentrations levels at steady state for osimertinib and AZ5104 in cerebrospinal fluid.
7. OSIBOOST 2-B: ctDNA analysis of cerebrospinal fluid.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Hospital Maastricht

Sponsor organisation

University Hospital Maastricht

Address

P Debyelaan 25

City

Maastricht

Postcode

6229 HX

Country

Netherlands

Scientific contact point

Organisation

University Hospital Maastricht

Contact name

Sander Croes

Public contact point

Organisation

University Hospital Maastricht

Contact name

Sander Croes

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications